Project Summary Abstract In addition to the pain and suffering they cause, the fiscal cost of neuropathic diabetic foot ulcers (DFUs) is estimated to be over $12 billion/year. Each year over 80,000 limb amputations are performed because current therapy is ineffective. Chronic infections, often residing in biofilms are implicated in the failure of DFUs to heal. Riptide Bioscience Inc. has developed novel designed Host Defense Peptides (dHDPs ) with demonstrated bactericidal activity and the ability to eradicate bacteria in biofilm. Designed host defense peptides are derived from naturally occurring HDPs that are ubiquitous in nature and provide the first line of defense against invading pathogens. In this proposal three dHDPs with broad based efficacy will be evaluated. A splinted wound model on diabetic mice will be infected with bioluminescent strains of S.aureus or P.aeurginosa. Bactericidal activity will be followed in real time by an animal fluorescence imaging system (Xenogen IVIS). Rates of wound closure and revascularization will be assessed. From these studies we will select a compound to undergo appropriate regulatory-enabling studies with a Phase II SBIR that could lead to a commercially viable therapeutic for the treatment of diabetic foot ulcers. .